tbuckley/cabot-search huggingface dataset:
Corrigendum to “Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials” [Eur Urol. 2023;84:393–405]
Authors: Pramit Khetrapal, Joanna Kae Ling Wong, Wei Phin Tan, Thiara Rupasinghe, Wei Shen Tan, Stephen B. Williams, Stephen A. Boorjian, Carl Wijburg, Dipen J. Parekh, Peter Wiklund, Nikhil Vasdev, Muhammad Shamim Khan, Khurshid A. Guru, James W.F. Catto, John D. Kelly
Journal: European Urology (2023)
PB1730: PROGNOSTIC VALUE OF EARLY T-ALL IMMUNOPHENOTYPES IN ADULTS ON THE RALL-2016 PROTOCOL
Authors: Anastasia Vasileva, Olga Aleshina, Galina Isinova, Ekaterina Kotova, Elena Paravichnikova
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: T-ALL is 25% of all cases of ALL in adults. Since 2017, a new variant of T-ALL – early T-cell precursors (ETP) ALL has been selected. ETP is characterized by its unique immunophenotype (absence of CD1a and CD8 expression, low (<75%) CD5 expression with the obligatory presence of one or more several markers of stem cells or myeloid precursors), by an unfavorable prognosis and a high risk of relapse. Aims: To analyze the survival rate in patients with T-ALL receiving therapy according to the protocol RALL-2016, depending on the variant, as well as to evaluate the effect of the complex karyotype (CK) on the prognosis and risk of relapse. Methods: From December 2016 to June 2022, 94 patients with a diagnosis of T-ALL/lymphoblastic lymphoma were included. Of these, 67 (71%) were male, 37 (39%) were female. Distribution by variants: 19 (20%) - ETP, 8 (8.5%) – near-ETP, 22 (23.5%) – TI/II, 40 (42.5%) – TIII, 5 (5.5%) – TIV. Results: There was no significant difference in median age in all groups, it ranged from 30 (in the ETP) to 37 (in the near-ETP) years. The median of leukocytes was the highest in the TIII (109 × 109/L), and the lowest in the near-ETP (30 × 109/L). The median LDH value was highest in the TIII (2690 IU/L). The number of patients with mediastinal tumors in the group with earlier variants of the disease was lower (in the ETP – 44%, in the TIV – 75%), while they had a neuroleukemia much more often (in the ETP – in 5 patients (26%), in the TIV – was not found). Abnormal karyotype (AK) was most common in the ETP (13 patients – 72%) and TIII (17 patients – 56%) variants of diseases. At the same time, CK was detected only in 2 patients (11%) from TIII. The overall 3-year survival (OS) rate was ETP – 40 %, near-ETP – 71,5%, TI/II – 56%, TIII – 86%, TIV – 60%. The relapse-free survival rate was – ETP - 54%, near-ETP – 33%, TI/II – 79%, TIII – 89%, TIV – 75% (figure 1). OS in the group with AK was 62%, in the group with normal – 80% (p=0.097), in the group with CK was 30%, in the group with any other abnormal – 79% (p=0.00017). Figure 1Summary/Conclusion: ETP is an unfavorable variant of the disease that requires intensification of therapy with the inclusion of allogeneic transplantation in the first remission. Early variants of YALL are characterized by a high recurrence rate during standard chemotherapy. The data received incline to consider patients with near-ETP and CK as candidates for more intensive therapy used in patients with ETP. Keywords: Immunophenotype, T cell acute lymphoblastic leukemia, Acute lymphoblastic leukemia, Acute leukemia
PB2393: ACTIVATION OF ER STRESS AND UNFOLDED PROTEIN RESPONSE (UPR) PATHWAYS IN HEPATITIS B VIRUS (HBV) INFECTED B CELLS AND ITS SIGNIFICANCE IN PATHOGENESIS OF B-CELL NON-HODGKIN LYMPHOMAS (B-NHL)
Authors: Mihaela Uta, Alina Ghionescu, Codruta Delia Popa, Norica Nichita, Daniel Coriu
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Hepatitis B virus (HBV) is an oncogenic virus known to contribute to hepatocellular carcinoma (HCC) development through a variety of mechanisms such as activation of the innate immune response triggering inflammatory signaling in liver cells; integration of HBV-DNA into the host genome, leading to genetic modifications; the ER stress induced by accumulation of viral proteins and the modulation of signaling pathways involved in cell cycle and proliferation by viral proteins. The scientific evidence is mainly focused on its implication in hepatic cancer, but several clinical and epidemiological studies support a role for HBV in extrahepatic diseases, such as B-cell non-Hodgkin lymphoma (B-NHL) occurrence. However, the mechanistic association between the HBV infection, the onset and progression of lymphoma remains unclear at the moment. Aims: The aim of our work is to investigate the potential role of HBV in lymphomagenesis by activating the endoplasmic reticulum (ER) stress and modulate the Unfolded Protein Response (UPR) signaling pathways. Methods: IM-9 cells (ATCC) were exposed to infectious HBV particles in order to investigate the ability of B lymphocytes to sustain productive HBV replication. HBV infection was assessed by qPCR, western blotting and ELISA. Regulation of UPR cellular signaling pathways IRE1α (Inositol-Requiring Enzyme 1), the transcription factor ATF6α and protein kinase PERK were evaluated by western blotting and RT-PCR. Results: Detection of HBV viral proteins, the accumulation of subviral and infectious particles in the B lymphocyte cell line suggest an active HBV replication, results confirmed by the binding assays of specific HBV entry inhibitors (myrcludex). IRE1α and ATF6α protein expression levels are overexpressed in HBV-infected B cells, while the expression of PERK proteins was not changed. A key regulator of tumorigenesis, the active form of XBP1 (spliced XBP1) mRNA generated from unspliced form by IRE1 during UPR was also increased in HBV infected cells. Summary/Conclusion The results obtained reveal new information regarding the etiology of HBV infection and potential mechanisms involved in the malignant transformation of B lymphocytes, information that may facilitate identification of new potential B-NHL triggers. Keywords: Hepatitis B virus, Lymphomagenesis, B cell lymphoma, B lymphocyte
PB1885: PHASE 1 STUDY OF ZIFTOMENIB IN COMBINATION WITH VENETOCLAX, VENETOCLAX/AZACITIDINE, OR STANDARD INDUCTION (7 + 3) CHEMOTHERAPY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
Authors: Amer M Zeidan, Amir Fathi, Ghayas Issa, Harry Erba, Julie Ahsan Mackey, Daniel Corum, Blake Tomkinson, Tom Kozlek, Mollie Leoni, Eunice Wang
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Relapsed or refractory (R/R) acute myeloid leukemia (AML) with nucleophosmin 1-mutations (NPM1-m) or KMT2A-rearrangment (KMT2A-r) represent a high unmet need. Ziftomenib is a potent and selective inhibitor that targets the menin-mixed-lineage leukemia (MLL) lysine[K]-specific methyltransferase 2A (KMT2A) interaction driving leukemogenesis in these subtypes. An ongoing Phase 1/2 study (KO-MEN 001) has demonstrated meaningful clinical activity and tolerability with ziftomenib monotherapy in R/R AML. In preclinical testing, ziftomenib combined with venetoclax induced synergistic lethality in KMT2A-r and NPM1-m human AML cell lines and patient-derived cells. Moreover, treatment with ziftomenib plus venetoclax/azacitidine has induced prolonged durable remissions in mice with KMT2A-r AML xenografts. Therefore, administration of ziftomenib in combination with standard-of-care (SOC) therapies may provide additional clinical benefit for patients with newly diagnosed or R/R NPM1-m and KMT2A-r menin-dependent AML Aims: KOMET-007 (KO-MEN-007, NCT# 05735184) is a 2-part dose escalation (Phase 1a) and expansion (Phase 1b) study to evaluate the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with non-intensive chemotherapy (NIC) and intensive chemotherapy (IC) in patients with NPM1-m and KMT2A-r AML. Methods: During Phase 1a, the ziftomenib dose will be escalated with standard doses of either venetoclax and azacitidine (zifto/ven/aza) or cytarabine and daunorubicin (zifto/7 + 3) in defined genetic cohorts (NPM1-m and KMT2A-r) using a rule-based approach (n=6 per cohort/dose level) to select ziftomenib doses for expansion/validation in Phase 1b. The Phase 1b portion will also evaluate zifto/ven/aza in newly diagnosed AML (KMT2A-r and NPM1-m) and zifto/ven in R/R AML (NPM1-m only). Results: The overall primary objectives are to determine the minimum biologically effective dose, dose-limiting toxicities, and recommended Phase 2 dose of ziftomenib combined with NIC and IC backbones in each genetically defined cohort. Secondary endpoints include preliminary antileukemic efficacy (including MRD-negative responses and number of patients able to transition to subsequent allogeneic stem cell transplant), pharmacokinetics, and pharmacodynamics. Exploratory endpoints include biomarkers for efficacy, resistance, and pharmacodynamics, and for activity in isolated myeloid sarcoma. Summary/Conclusion: KOMET-007 will determine the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with non-intensive chemotherapy and intensive chemotherapy in newly diagnosed or R/R patients with NPM1-m and KMT2A-r AML. Keywords: AML, Venetoclax, Induction chemotherapy, relapsed/refractory
P1681: RACIAL DIFFERENCES IN DETERMINANTS OF TREATMENT DECISION-MAKING AMONG PATIENTS WITH MULTIPLE MYELOMA
Authors: Lisa Dwyer, Dee Lin, Bingcao Wu, Noa Biran, Beth Faiman, Jennifer Ahlstrom, Peter Herout, Kathleen Deering, Margaret Yung, Victoria Kulbokas, Josh Feldman, Erika D Kline, Thomas W Leblanc
Journal: HemaSphere (2023)

Topic: 35. Quality of life and palliative care Background: Effective shared decision-making incorporates patients’ goals, values, and preferences alongside clinical factors and other considerations. Aims: We aimed to describe differences in patient preferences regarding treatment decision roles, communication styles, goals, and other determinants of decision-making between Black patients (BP) and White patients (WP) with multiple myeloma (MM). Methods: A survey was conducted with adult patients recruited from online MM patient support communities in the US between 9/2022 and 11/2022. Survey items were informed by a targeted literature review, qualitative interviews, and a steering committee of clinical experts, patients, and a caregiver representative. Descriptive statistics were generated, reported in aggregate, and stratified by race. Results: Of the 126 patients who completed the survey, 86 (68%) identified as WP and 30 (24%) as BP. A higher proportion of WP than BP reported being referred to a MM specialist upon diagnosis (56% vs 40%); 33% of BP were referred after their first or second relapse. Patients in both groups reported similar time spent by their physicians providing information about MM treatment. 47% and 22% of BP and WP, respectively, preferred that the physician have a greater role in deciding on MM treatments than themselves. 40% of BP preferred a shared role vs 50% of WP, while 27% of BP and 43% of WP felt they had shared involvement (Table). Duration of response and quality of life (QoL) were the most important treatment attributes for all patients. Of the other ranked treatment attributes (lower score = higher rank), risk of side effects and death from treatment were more important to WP (mean, 2.9 WP vs 5.1 BP), while administration route (6.7 WP vs 5.9 BP) and need for monitoring (7.3 WP vs 5.0 BP) were more important to BP. Both BP and WP indicated they would prefer better future health over better present health, but BP showed a preference toward length of life while WP showed a preference toward QoL. The ability to work or earn money, treatment anxiety, and spiritual/cultural background were among the factors that were more important to BP than to WP when making treatment decisions. Summary/Conclusion: BP and WPs with MM place different importance on their roles and key attributes considered in treatment decision-making. Findings suggest that physicians demonstrate bias by taking a greater role, versus shared involvement, in decision-making with BP. Physicians should consider differences in personal values and preferences of patients from different racial backgrounds as they approach MM treatment discussions with patients.Keywords: Multiple myeloma, Patient, Race, Real world data
P1629: DISCONTINUATION OF TREATMENT WITH THROMBOPOIETIN RECEPTOR AGONISTS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA: A SINGLE-CENTER CLINICAL EXPERIENCE
Authors: Ana María Mena Santano, Patricia Tejuca González, Francisco José López Jaime, Rubén Clavero López, Adrián Montaño, Ihosvany Fernández Bello
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Thrombopoietin receptor agonists (TPO-RAs) are valuable therapeutic tools in the management of patients with immune thrombocytopenia (ITP). There is growing evidence that TPO-RAs can trigger sustained response in some patients after tapering and discontinuation but data are still scarce. Aiming to bring more elements to this issue, we study a cohort of patients subjected to TPO-RAs discontinuation in our hospital. Aims: TPO-RAs discontinuation in patients with ITP treated in our hospital were analysed. Methods: Retrospective and observational study in adult ITP patients who underwent discontinuation of TPO-RAs in our hospital was performed. Criteria for tapering initiation and subsequent discontinuation was a platelet count ≥ 50 × 109/L for at least six consecutive months. Results: Thirty-three ITP patients (54.5% women) initiated TPO-RA discontinuation at a median (IQR) age of 52.1 (29.7-65.8) years old. In total, 57.6% received TPO-RA alone during the TPO-RA treatment period. The platelet count at the time of initiation of tapering was 203 (125-518) × 109/L. In 69.7 % of the patients, the discontinuation was carried out successfully throughout 872 (470-1264) days with a platelet count of 194 (113-247) × 109/L. Only 30.3% patients had to restart treatment after 480 (17-1170) days from discontinuation due to severe thrombocytopenia and/or bleeding. However, all patients responded successfully to rescue treatment with the same analogue. There was no evidence of thrombotic events among the patients. Summary/Conclusion: Our results support that the discontinuation of TPO-RAs following the current recommendations was safe and effective to maintain platelet count ≥ 50 × 109/L in a high proportion of the studied patients until the time this work is presented. Wider and longer studies are needed to reach more robust and extensible conclusions in this clinical field. Keywords: Platelet count, Immune thrombocytopenia (ITP), Thrombopoietin (TPO), Anti-platelet antibody
P544: SINGLE-SYSTEM UNIFOCAL ADULT LANGERHANS CELL HISTIOCYTOSIS: A SINGLE-CENTER RETROSPECTIVE STUDY
Authors: Min Lang, Hua-Cong Cai, He Lin, Long Chang, Jia-Wen Dai, Jia Chen, Jian LI, Ming-Hui Duan, Dao-Bin Zhou, Xin-Xin Cao
Journal: HemaSphere (2023)

Background: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system(SS) and multiple system(MS) according to clinical site of involvement. There are few studies related to single-system unifocal adult LCH currently. Aims: Objective of this single-center retrospective study is to describe the clinical features, affected organs, gene mutations, treatment and prognosis of adult single-system unifocal LCH patients. Methods: This retrospective study included patients ≥14 years old, and diagnosed with single-system unifocal LCH in Peking Union Medical College Hospital (Beijing, China) from September 2001 to December 2022. Results: Overall 109 patients were enrolled in this study, with a 2.03:1 male to female ratio. Median age at diagnosis was 33 years (14-69). The most common clinical manifestations were bone pain, accounting for 30.3%, followed by cough (11.0%) and diabetes insipidus (11.0%). The most common organs involved were bone (53.2%), followed by lung (18.3%), pituitary (10.1%), lymph nodes (5.5%), skin (2.8%), liver (2.8%) and thyroid (0.9%). Among the 20 patients with lung involvement, 17 patients had smoking history. The frequency of BRAFV600E mutation, MAP2K1 mutation and BRAFindel mutation were 24.3%, 10.8% and 2.7% respectively. BRAFV600Emutations and MAP2K1 mutations were independent of the type of organ involved and were not associated with OS and PFS. As for first-line treatment, 48 had surgery, 15 had radiotherapy, 16 were suggested observation, 9 had chemotherapy. All of the 20 patients with lung involvement were suggested to quit smoking. After a median follow-up time of 43.2 months (0.2-246.6), 3 patients died of respiratory failure, and the estimated 3-year overall survival (OS) was 98.7%. 24 patients developed disease progression, of which 5 had local recurrence, 4 progressed to single system multiple lesions (SS-M) and 15 progressed to MS, and the estimated 3-year progression-free survival (PFS) was 79.0%. Progression rate of pituitary involvement was the highest, 45.5% (5/11), followed by lymph node 33.3% (2/6), lung 20.0% (4/20) and bone 19.0% (11/58) (Figure 1). Univariate analysis showed that patients whose age at diagnosis ≤30 years had significant shorter PFS than those older than 30 years (the estimated 3-year PFS 89.1% vs 66.9%, p =0.039). Summary/Conclusion: In this study, we report a large series of single-system unifocal adult LCH patients. Bone is the most commonly involved organ. The overall survival of single-system unifocal adult LCH is good，and more than 30 years at diagnosis indicate good PFS.Figure1: Progression pattern of each affected organ（N=106） Keywords: Adult, Langerhans Cell Histiocytosis
P1093: MATCHING-ADJUSTED INDIRECT COMPARISON (MAIC) OF ZANUBRUTINIB (ZANU) VERSUS IBRUTINIB (IBRU) IN RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA (R/R MZL)
Authors: Catherine Thieblemont, Kaijun Wang, Sam Keeping, Ina Zhang, Keri Yang, Boxiong Tang, Leyla Mohseninejad
Journal: HemaSphere (2023)

Topic: 36. Ethics and health economics Background: ZANU is a Bruton tyrosine kinase inhibitor (BTKi) that has been evaluated for the treatment of R/R MZL in two phase 2, single-arm trials (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. IBRU, a first-generation BTKi, has also been evaluated for R/R MZL in a phase 2, single-arm trial (PCYC-1121, n=60 [Noy et al., Blood 2017; Noy et al., Blood Adv 2020]). Aims: Here, we conducted an unanchored MAIC to estimate the comparative efficacy of ZANU versus IBRU in R/R MZL. Methods: The MAIC utilized study-level data from PCYC-1121 and pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. A logistic propensity score model was used to estimate weights for patients in the ZANU trials so that weighted mean baseline characteristics matched those in PCYC-1121. The following characteristics were identified as key prognostic factors and included in the base case propensity score model: number of prior lines of therapy, MZL subtype, response to prior therapy, and age. A sensitivity analysis was conducted including additional characteristics (B symptoms, time since last therapy, prior anti-CD20 therapy, bulky disease [>5cm], and lactate dehydrogenase above normal). Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs). Results: After applying weights estimated from the base case propensity score model, the effective sample size (ESS) for ZANU was 68 (Table). Compared with IBRU, ZANU significantly reduced the risk of progression (HR 0.38; 95% CI 0.21–0.69, P=0.001) and was associated with a higher ORR (OR 2.37; 95% CI: 1.13–4.96, P=0.022). OS was comparable for ZANU and IBRU, which is consistent with expected survival for indolent lymphomas. The sensitivity analysis accounting for additional prognostic factors suggested the two treatments were comparable across all outcomes, owing in part to the low ESS (24) for ZANU associated with the expanded model. A leave-one-out analysis showed improved PFS (HR 0.33–0.45) for ZANU when excluding B symptoms, time since last therapy, or bulky disease from the expanded model. Summary/Conclusion: This MAIC demonstrated ORR and PFS benefits for ZANU versus IBRU in R/R MZL.Keywords: Indolent non-Hodgkin’s lymphoma, Marginal zone, relapsed/refractory, Tyrosine kinase inhibitor
P1215: CHARACTERIZATION AND CLINICAL SIGNIFICANCE OF T FOLLICULAR HELPER SUBSETS IN FOLLICULAR LYMPHOMA
Authors: Zhi-Zhang Yang, Xinyi Tang, Hyo Jin Kim, Vaishali Bhardwaj, Prithviraj Mukherjee, Patrizia Mondello, Jose Villasboas, Anne Novak, Stephen Ansell
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: T follicular helper (TFH) cells are a subset of CD4+ T cells that reside within the follicles of secondary lymphoid organs and essential in the germinal center (GC) reaction. Follicular lymphoma (FL) is a GC-derived malignancy and malignant B cells play a crucial role in the development of the tumor microenvironment. Aims: Given TFH cells are a major subpopulation in the TME and phenotypically heterogenous, in this study, we wanted to characterize intratumoral TFH cells and to examine its clinical significance in FL. Methods: Single cell analysis of mass cytometry (CyTOF) and the Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) were performed. Antibody staining list includes 37 surface markers for both CyTOF and CITE-seq. Results: Transcriptomic and proteomic profiling analysis with CITE-seq (n=8) and CyTOF (n=82) revealed that TFH cells are phenotypically more heterogenous in FL than benign tonsil tissues (Fig.1A). Clustering analysis showed that TFH cells form subsets with unique phenotypes. The expression of many common markers including CXCR5, ICOS, IL-21, TOX2, CD57, GZMK, XCL1, XCL2, CXCL13 and CD40L varies on TFH subsets (Fig. 1B). Each FL patient showed different dominant TFH subsets, in contrast to tonsil donors which were highly homogenous. Some TFH subsets were only present in FL and absent in tonsil tissues, suggesting the existence of FL-specific TFH cells. Cytokines (IL-2, IL-12, IL-17 and IL-21) and activated B cells upregulated TFH markers including PD-1, CXCR5 and IL-21 to induce the development of TFH subsets such as IL-21+ or IL-21+IFN-γ+ TFH cells, which was inhibited by rapamycin, an immunosuppressor (Fig. 1C). We observed that the TFH cell frequency significantly correlated with the number of lymphoma B cells. Futhermore, while TFH cells as a whole showed no correlation with prognosis, TFH subsets such as CD57+ TFH cells were significantly associated with inferior patient outcomes. Using CITRUS analysis, we found that the abundance of CD57+ TFH clusters was higher in patients failed event-free survival at 24 months (EFS24) than those achieved EFS24 as well as patients with progression (Prog) than those with complete remission (CR) (Fig. D-E). Summary/Conclusion: Taken together, our results indicate that TFH cells are highly heterogenous in FL with some TFH subsets being tumor specific. We observed that CD57+ TFH subset is associated with inferior patient outcomes, suggesting a detrimental role of this subset in FL.Keywords: T cell, Lymphoma, Tumor immunology, Follicular lymphoma